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El Andaloussi Group

Development of delivery vectors for therapeutic nucleic acids and proteins

Biological action of exosomes and their uptake into recipient cells

The research group focuses on comparing different antisense oligonucleotide (AO) chemistries used to interfere with gene expression and try to correlate differences in activity to their ability to internalise cells in vitro and in vivo. We are also interested in developing peptide- and exosome-based delivery vectors to improve the delivery of AOs and other macromolecular drugs.

Our research could be divided into two broad areas; 1) Development of therapeutic AOs and drug delivery vectors for translational gene therapy applications and 2) Characterization and exploitation of biological nanovesicles, namely exosomes, for therapeutic applications.

Using various biochemical approaches, we try to understand how AOs interact with cell surface components and intracellular proteins and how different backbone chemistries of AOs influence these interactions and subsequent cellular activity. By improving this understanding, we hope to be able to design new “smarter” AOs with physicochemical properties that promote productive cellular uptake and greater therapeutic activity. A parallel approach taken is also on the development of peptide-based nanoparticle delivery systems that are used to further improve the bioavailability of therapeutic AOs and other macromolecular drugs.

The other arm of our research focuses on the characterisation and exploitation of cell-secreted extracellular vesicles termed exosomes. We are particularly interested in understanding how and which RNAs and proteins are sorted into exosomes and how they can influence recipient cells. In order to fully understand the biological significance of exosomes, we have developed a purification method that is able to fractionate the secretome of cells and distinguish proteins and RNAs in exosomes from RNA associated with extracellular protein complexes. These studies are primarily conducted in embryonic stem (ES) cells, neuronal cells and muscle cells. As our ultimate goal is to exploit these exosomes for therapeutic delivery of RNA and proteins, understanding their composition is of utmost importance as it will enable us to devise methods for engineering cells to produce exosomes which can contain our therapeutic cargo of interest. In conclusion, the work in our lab ranges from basic cell biology and organic synthesis to application of new chemical and biological entities in various neurological disease models.